This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Anoikis is defined as apoptosis that is inhibited by extracellular matrix; it was discovered by our laboratory and reported in a 1994 Journal of Cell Biology paper. We are focusing on the mechanisms by which the oncogenic EMT (epithelial-to-mesenchymal transition) confers resistance to anoikis upon carcinoma cells. In particular, we are investigating the role of ankyrins, cytoskeletal proteins that link the actin cytoskeleton to various transmembrane adhesion receptors including E-cadherin. We hypothesize that ankyrin expression in normal epithelial cells sets up a transcriptional program that permits cells to die in response to cell-matrix detachment. Conversely, we posit that the loss of ankyrin that occurs frequently in carcinoma cells establishes an anoikis-resistance gene expression program. This project addresses these hypotheses